soluble fusion protein
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2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Marie Westermann ◽  
Anke Baranowsky ◽  
Giorgia Di Lorenzo ◽  
Tatyana Danyukova ◽  
Jamie Soul ◽  
...  

AbstractSevere skeletal alterations are common symptoms in patients with mucolipidosis type II (MLII), a rare lysosomal storage disorder of childhood. We have previously reported that progressive bone loss in a mouse model for MLII is caused by an increased number of bone-resorbing osteoclasts, which is accompanied by elevated expression of the cytokine interleukin-6 (IL-6) in the bone microenvironment. In the present study we addressed the question, if pharmacological blockade of IL-6 can prevent the low bone mass phenotype of MLII mice. Since the cellular IL-6 response can be mediated by either the membrane-bound (classic signaling) or the soluble IL-6 receptor (trans-signaling), we first performed cell culture assays and found that both pathways can increase osteoclastogenesis. We then crossed MLII mice with transgenic mice expressing the recombinant soluble fusion protein sgp130Fc, which represents a natural inhibitor of IL-6 trans-signaling. By undecalcified histology and bone-specific histomorphometry we found that high circulating sgp130Fc levels do not affect skeletal growth or remodeling in wild-type mice. Most importantly, blockade of IL-6 trans-signaling did neither reduce osteoclastogenesis, nor increase bone mass in MLII mice. Therefore, our data clearly demonstrate that the bone phenotype of MLII mice cannot be corrected by blocking the IL-6 trans-signaling.


2019 ◽  
Vol 27 (11) ◽  
pp. 1906-1918 ◽  
Author(s):  
Yonghui Zhang ◽  
Hailin Zhang ◽  
Mei Wei ◽  
Tao Mou ◽  
Tao Shi ◽  
...  

2018 ◽  
Vol 1860 (9) ◽  
pp. 1681-1686 ◽  
Author(s):  
Miriam A. Kael ◽  
Daniel K. Weber ◽  
Frances Separovic ◽  
Marc-Antoine Sani

Immunology ◽  
2016 ◽  
Vol 148 (1) ◽  
pp. 40-55 ◽  
Author(s):  
Daniel Perez-Witzke ◽  
María Auxiliadora Miranda-García ◽  
Nuris Suárez ◽  
Raquel Becerra ◽  
Kharelys Duque ◽  
...  

2013 ◽  
Vol 5 ◽  
pp. CMT.S8921 ◽  
Author(s):  
Michael W. Stewart

The treatment of exudative age-related macular degeneration (AMD) has been completely transformed by the development of drugs that bind vascular endothelial growth factor (VEGF). The antibody-based VEGF inhibitors bevacizumab and ranibizumab usually prevent the enlargement of choroidal neovascular membranes, reduce vascular permeability, and improve visual acuity. The newest VEGF inhibitor, aflibercept, is a soluble fusion protein that binds all isoforms of VEGF-A, VEGF-B, and placental growth factor with high affinity. Preclinical studies demonstrated aflibercept's ability to prevent experimental neovascularization and tumor growth in animal models. In phase 3 trials for exudative AMD, patients who received aflibercept avoided moderate vision loss and experienced improved visual acuity comparable to those who received ranibizumab. Additionally, patients who were treated with aflibercept 2 mg every 8 weeks (after 3 monthly loading doses) had similar visual results to those treated every 4 weeks. When treated as needed during the second year of the trials, patients were able to last an average of 3 months between aflibercept injections. Since its regulatory approval, aflibercept has also been found to perform well as a salvage therapy for eyes that respond incompletely to ranibizumab and bevacizumab. Because aflibercept can be administered less frequently than ranibizumab, it promises to decrease the frequency of patients’ visits to physicians’ offices in addition to the overall cost of AMD therapy.


Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1850-1860 ◽  
Author(s):  
Sophie C. Egea ◽  
Ian M. Dickerson

Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates with CLR signaling and CGRP efficacy. It is not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it coimmunoprecipitated with RCP and inhibited signaling from endogenous CLR. Expression of this dominant-negative domain of CLR did not significantly inhibit trafficking of CLR to the cell surface, and thus RCP may not have a chaperone function for CLR. Instead, RCP may regulate CLR signaling in the cell membrane, and direct interaction between RCP and CLR is required for CLR activation. To date, RCP has been found to interact only with CLR and represents a novel neuroendocrine regulatory step in GPCR signaling.


2008 ◽  
Vol 198 (6) ◽  
pp. 836-842 ◽  
Author(s):  
Julie A. Pavlin ◽  
Andrew C. Hickey ◽  
Nancy Ulbrandt ◽  
Yee‐Peng Chan ◽  
Timothy P. Endy ◽  
...  

2005 ◽  
Vol 2 (2) ◽  
pp. 107-111 ◽  
Author(s):  
Jiang Chang-Jun ◽  
Li Yuan-Hua ◽  
Fang Wan-Ping

AbstractThe β-glucosidase gene has important effects on alcoholic aroma precursors and insect resistance of the tea plant [Camellia sinensis (L.) O. Kutze]. The complete cDNA sequence of β-glucosidase of the tea plant was cloned; its full length was 1475 bp, and shared 40–60% similarity with corresponding parts of the nucleotide sequence of β-glucosidase gene from other plants. Its secondary structure contains 14.33% α-helix, 25.43% β-pleated sheet and many functional amino acid domains. The β-glucosidase gene was cloned into the pET-32a expression system and expressed at high-efficiently in Escherichia coli BL21 (DE3); the molecular weight of expressed fusion protein was 63 kDa. The results of enzymic reaction showed that the fusion protein possessed normal bioactivity, and it could catalyse the dehydration of the glycosidic bond. The soluble fusion protein was expressed mainly in the cytoplasm.


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